Long-Term but not Short-Term Cardioprotection can be Induced by Preconditioning in Hypercholesterolemia

Abstract

Preconditioning of the heart by single or multiple noninjurious ischemic stimuli may induce both short-term (up to 2 hours) and long-term (3 to 24–48 hours) cardiac protection against the consequences of a subsequent severe stress. Up to now, however, both short-term and long-term protection has been demonstrated only in normal, metabolically healthy animals.

Therefore, the aim of the study reported in this chapter was to test whether short-term and long-term (delayed) carhac protection could be induced under conditions of experimental atherosclerosis in hypercholesterolemic rabbits that had been fed a cholesterol-rich diet over two months, Repeated brief periods of rapid ventricular pacing were used to induce delayed protection of the heart. Moderation of postpacing right intracavitary ST-segment elevation and of left ventricular end-diastolic pressure (both produced by ventricular overpacing at 500 beats/min for 15 minutes) was found both in normal animals and in those fed a cholesterol-rich diet. However, the short-lived protection induced by a single preconditioning pacing was present only in healthy, normal animals. The cardioprotective effect of short-term preconditioning appeared in parallel with an attenuation of the ischemia-induced increase in cardiac CAMP content measured by radioimmunoassay. The same parallel could be observed in delayed carhoprotection in both normal and hypercholesterolemic rabbits. An increase in cardiac cGMP content was characteristic of short-term but not of long-term protection. These results suggest that the delayed cardiac protection evoked by multiple brieE, rapid pacing operates even in hypercholesterolemia-induced experimental atherosclerosis but that the short-term protection evoked by a single pacing period is lost in hypercholesterolemic rabbits.